Chronic Idiopathic Constipation
Conditions
Brief summary
The purpose of this study is to evaluate the bioequivalence of sprinkle and capsule formulations of lubiprostone, as compared to placebo, when administered orally in participants with Chronic Idiopathic Constipation (CIC).
Interventions
DRUGLubiprostone
24 mcg administered orally BID
DRUGPlacebo
24 mcg administered orally BID
Sponsors
Sucampo AG
Sucampo Pharmaceuticals, Inc.
Sucampo Pharma Americas, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Either has medically-confirmed diagnosis of chronic constipation (per Rome III), or meets the diagnosis as confirmed using the Rome III constipation module questionnaire during the Screening period. * Is male or female, 18 or older years of age * Should be on stable dose of fiber supplement or a concomitant medication for the indication of lowering blood pressure
Exclusion criteria
* Has any gastrointestinal (GI) condition, other than constipation, affecting GI motility or defecation * Is unable to eat or drink, take oral medications, or to hold down oral medications due to vomiting
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Observed Spontaneous Bowel Movement (SBM) Count Within 1 Week | during the 1-week treatment period | Observed SBM count was based on the observed data reported in the electronic daily diary for the actual number of SBMs during the 1-week treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From first dose of study medication to follow-up (up to 15 days) | An adverse event (AE) is any untoward medical occurrence (including clinically significant changes in laboratory values or other clinical tests) experienced by a participant administered a pharmaceutical product regardless of causal relationship with the treatment. A TEAE is an episode which occur after the administration of the first dose of study medication and within 7 days after final dose. |
| Mean SBM Consistency Score Within 1 Week | during the 1-week treatment period | Stool consistency associated with SBMs was rated according to the 7-point Bristol Stool Form Scale (1-7) where 1 = Separate hard lumps, like nuts (hard to pass), 2 = Sausage-shaped but lumpy, 3 = Like a sausage but with cracks on the surface, 4 = Like a sausage or snake, smooth and soft, 5 = Soft blobs with clear-cut edges (passed easily), 6 = Fluffy pieces with ragged edges, a mushy stool, 7 = Watery, no solid pieces; entirely liquid. Scores in the mid-range of this scale indicate better stool consistency. |
| Mean SBM Straining Score Within 1 Week | during the 1-week treatment period | Bowel straining associated with SBMs was rated on a scale of 0-4 where 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Very severe. Higher score indicates more straining, so a worse condition. |
Countries
United States
Participant flow
Recruitment details
This trial was conducted at 66 investigative sites in the United States.
Pre-assignment details
Actual randomization ratio of sprinkle:placebo:capsule (2:1:1) was different than the planned randomization ratio (1:1:1)
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matching to lubiprostone (sprinkle/capsule) twice daily (BID) for 7 days. | 126 |
| Lubiprostone Sprinkle Lubiprostone 24 mcg sprinkle BID for 7 days. | 234 |
| Lubiprostone Capsule Lubiprostone 24 mcg capsule BID for 7 days. | 113 |
| Total | 473 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 8 | 4 |
| Overall Study | Investigator Decision | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 7 | 1 |
| Overall Study | Reason not provided | 3 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 5 | 3 |
Baseline characteristics
| Characteristic | Placebo | Lubiprostone Sprinkle | Lubiprostone Capsule | Total |
|---|---|---|---|---|
| Age, Continuous | 46.7 years STANDARD_DEVIATION 13.32 | 47.4 years STANDARD_DEVIATION 13.17 | 48.8 years STANDARD_DEVIATION 13.38 | 47.6 years STANDARD_DEVIATION 13.25 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 31 Participants | 64 Participants | 33 Participants | 128 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 95 Participants | 170 Participants | 80 Participants | 345 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 12 Participants | 3 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 50 Participants | 99 Participants | 48 Participants | 197 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 71 Participants | 120 Participants | 59 Participants | 250 Participants |
| Sex: Female, Male Female | 105 Participants | 202 Participants | 92 Participants | 399 Participants |
| Sex: Female, Male Male | 21 Participants | 32 Participants | 21 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 143 | 0 / 275 | 0 / 130 |
| other Total, other adverse events | 15 / 143 | 50 / 275 | 29 / 130 |
| serious Total, serious adverse events | 0 / 143 | 0 / 275 | 0 / 130 |
Outcome results
Primary
Observed Spontaneous Bowel Movement (SBM) Count Within 1 Week
Observed SBM count was based on the observed data reported in the electronic daily diary for the actual number of SBMs during the 1-week treatment period.
Time frame: during the 1-week treatment period
Population: Per protocol population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Observed Spontaneous Bowel Movement (SBM) Count Within 1 Week | Week 1 | 3.68 SBMs/week | Standard Deviation 2.164 |
| Placebo | Observed Spontaneous Bowel Movement (SBM) Count Within 1 Week | Baseline | 1.38 SBMs/week | Standard Deviation 0.692 |
| Lubiprostone Sprinkle | Observed Spontaneous Bowel Movement (SBM) Count Within 1 Week | Baseline | 1.37 SBMs/week | Standard Deviation 0.693 |
| Lubiprostone Sprinkle | Observed Spontaneous Bowel Movement (SBM) Count Within 1 Week | Week 1 | 4.82 SBMs/week | Standard Deviation 3.658 |
| Lubiprostone Capsule | Observed Spontaneous Bowel Movement (SBM) Count Within 1 Week | Baseline | 1.35 SBMs/week | Standard Deviation 0.72 |
| Lubiprostone Capsule | Observed Spontaneous Bowel Movement (SBM) Count Within 1 Week | Week 1 | 5.74 SBMs/week | Standard Deviation 3.786 |
p-value: =0.002ANCOVA
Comparison: Treatment p-value is from ANCOVA using SBM count as dependent variable, treatment as fixed effect and baseline count as random effectp-value: <0.0001ANCOVA
Secondary
Mean SBM Consistency Score Within 1 Week
Stool consistency associated with SBMs was rated according to the 7-point Bristol Stool Form Scale (1-7) where 1 = Separate hard lumps, like nuts (hard to pass), 2 = Sausage-shaped but lumpy, 3 = Like a sausage but with cracks on the surface, 4 = Like a sausage or snake, smooth and soft, 5 = Soft blobs with clear-cut edges (passed easily), 6 = Fluffy pieces with ragged edges, a mushy stool, 7 = Watery, no solid pieces; entirely liquid. Scores in the mid-range of this scale indicate better stool consistency.
Time frame: during the 1-week treatment period
Population: PP population. Number of participants analysed indicates participants who were evaluated for this outcome measure at each categorical time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean SBM Consistency Score Within 1 Week | Baseline | 2.47 score on a scale | Standard Deviation 1.122 |
| Placebo | Mean SBM Consistency Score Within 1 Week | Week 1 | 3.43 score on a scale | Standard Deviation 1.27 |
| Lubiprostone Sprinkle | Mean SBM Consistency Score Within 1 Week | Baseline | 2.39 score on a scale | Standard Deviation 1.211 |
| Lubiprostone Sprinkle | Mean SBM Consistency Score Within 1 Week | Week 1 | 3.94 score on a scale | Standard Deviation 1.516 |
| Lubiprostone Capsule | Mean SBM Consistency Score Within 1 Week | Baseline | 2.28 score on a scale | Standard Deviation 1.045 |
| Lubiprostone Capsule | Mean SBM Consistency Score Within 1 Week | Week 1 | 4.22 score on a scale | Standard Deviation 1.409 |
Secondary
Mean SBM Straining Score Within 1 Week
Bowel straining associated with SBMs was rated on a scale of 0-4 where 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Very severe. Higher score indicates more straining, so a worse condition.
Time frame: during the 1-week treatment period
Population: PP population. Number of participants analysed indicates participants who were evaluated for this outcome measure at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean SBM Straining Score Within 1 Week | Baseline | 2.39 score on a scale | Standard Deviation 0.739 |
| Placebo | Mean SBM Straining Score Within 1 Week | Week 1 | 1.76 score on a scale | Standard Deviation 0.871 |
| Lubiprostone Sprinkle | Mean SBM Straining Score Within 1 Week | Baseline | 2.31 score on a scale | Standard Deviation 0.911 |
| Lubiprostone Sprinkle | Mean SBM Straining Score Within 1 Week | Week 1 | 1.45 score on a scale | Standard Deviation 0.937 |
| Lubiprostone Capsule | Mean SBM Straining Score Within 1 Week | Baseline | 2.40 score on a scale | Standard Deviation 0.892 |
| Lubiprostone Capsule | Mean SBM Straining Score Within 1 Week | Week 1 | 1.19 score on a scale | Standard Deviation 0.917 |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence (including clinically significant changes in laboratory values or other clinical tests) experienced by a participant administered a pharmaceutical product regardless of causal relationship with the treatment. A TEAE is an episode which occur after the administration of the first dose of study medication and within 7 days after final dose.
Time frame: From first dose of study medication to follow-up (up to 15 days)
Population: Safety population, defined as all randomized participants who took at least one dose of double-blinded study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 21 Participants |
| Lubiprostone Sprinkle | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 40 Participants |
| Lubiprostone Capsule | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 73 Participants |